Corticotropin-releasing factor (CRF), a key regulator of hypothalamus-pituitary-adrenal cortical (HPA) axis, is also a critical factor in coordinating autonomic, immunological and behavioral responses to stress. Recently, a novel CRF-like peptide, urocortin (Ucn) was identified. Its receptor binding affinity and distinct tissue distribution suggests tat it has unique developmental and physiological roles. We propose to study the tissue-specific expression of Ucn. The genomic sequence will be isolated for the Ucn gene and linked to a reporter gene. Ucn-expressing cell lines and tissues will be used as a model system to analyze the Ucn transcription elements that direct the tissue-specific expression of the reporter gene. The interaction between the transcription elements and their trans-acting factors will then be studied to reveal what factors act through these elements. Novel factors identified will be cloned and further analyzed. The role of tissue specific elements will also be confirmed using transgenic techniques.